This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Six Rhesus macaques (Macaca mulatta) previously vaccinated with VSV/SFV E660 and challenged with SIVsmE660 were treated with anti-CD8 antibody to perform in vivo CD8 depletions in July 2010 (290 days after the original viral challenge). The four animals that completely resisted infection had plasma virus loads that remained undetectable after CD8 depletion further supporting the idea of sterilizing immunity in these animals. The two animals that resolved their SIV infections had a resurgence of viral infection with peak viral loads slightly higher than those seen previously (5.5 and 6.7 log copies/ml after depletion versus 3.9 and 5.8 log copies/ml previously) in these two monkeys. To further test if the protection afforded by the original vaccination is long lasting and if the immune system can be re-activated with an additional vaccination after a long period of rest, five animals protected from the original viral challenge will be re-immunized and re-challenged in the coming year. All animals will continue to be monitored to follow the progression of infection or lack thereof. Additionally in this study we are utilizing the single genome analysis (SGA) technique to a) to characterize Env of the SIVsmE660 viral challenge stock-we have finished sequencing and calculated the stock diversity of the challenge E660 swarm;and b) to characterize the founder viruses from rhesus macaques vaccinated with VSV vaccines and challenged intra-rectally. The goal is to compare and contrast the founder viruses Env sequences originating from animals vaccinated with VSV-HA vaccine from the two animals that showed partial protection-with VSV-E660-Gag-Env vaccine. This work is currently in progress.